PRO 542: reduced viral loads in patients failing conventional therapy

Progenics Pharmaceuticals reported that its novel investigational drug, PRO 542, produced a significant antiviral response in HIV-infected individuals who were no longer responding to currently available antiretroviral medications.

In treatment-experienced patients, a single dose of PRO 542 reduced viral concentrations by 60% to 80% on average for up to four weeks. PRO 542 belongs to a new class of drugs, viral-entry inhibitors, which are designed to prevent HIV from entering and infecting cells. The findings were presented today at the 15th International Conference on Antiviral Research in Prague, The Czech Republic.

“PRO 542 showed important reductions in viral load in those patients who were most in need of new treatment options,” said Jeffrey M. Jacobson, M.D., Director, AIDS Center, Mount Sinai School of Medicine, New York City and Principal Investigator of the PRO 542 study in adults. “Conventional therapy is unable to control HIV long-term due to mutation of the virus. All currently available HIV drugs inhibit just two enzymes involved in viral replication after infection has occurred. PRO 542 is a viral-entry inhibitor which may provide clinical advantages over the current armamentarium. This novel antibody-like fusion protein is designed to work against all strains of HIV and to minimise the emergence of viral resistance. PRO 542 may prove particularly valuable for salvage therapy of patients failing conventional drug regimens.”

In clinical studies, PRO 542 was well tolerated and produced statistically significant (p=0.007) acute reductions in viral load across all seven patients who received a single 25 mg/kg intravenous infusion of the drug. These findings extend previous studies of four intravenous doses ranging to 10 mg/kg. In addition, an analysis of data from 22 adults treated with single-dose PRO 542 in a Phase I/II study identified a subgroup of patients who were the most highly responsive to therapy. These patients were failing conventional therapies and had evidence of advanced disease as measured by low numbers of CD4+ T cells (<200 cells/mm3) and/or high viral loads (>100,000 copies/mL) before treatment with PRO 542. CD4+ T cells are key components of the immune system and the major targets of HIV infection. The viral load reductions in these patients ranged from 0.4 to 0.8 log10 copies/mL, were dose-dependent, and were sustained for two to four weeks.

Viruses that are broadly resistant to currently available antiretroviral medications represent a growing challenge for HIV therapy. A study presented at the most recent Interscience Conference on Antimicrobial Agents and Chemotherapy reported that in the U.S. approximately 78% of HIV-infected individuals harbour virus that is resistant to one or more classes of antiretroviral agents, thus reducing their treatment options. An estimated one million Americans will be infected with HIV by the end of 2002.

“We have identified a group of patients who were not responding to currently available therapies but who did exhibit a significant antiviral response to PRO 542,” said Robert J. Israel, MD, Vice President of Medical Affairs at Progenics. “These findings are being incorporated into our Phase II clinical program. The company is also developing subcutaneous and intramuscular formulations of PRO 542 that may afford simplified dosing regimens.”

PRO 542 is an antibody-like molecule which is designed to neutralise HIV by directly binding to gp120, a protein on the surface of the virus, thereby preventing HIV attachment to healthy cells within the immune system. Whereas current antiretroviral medications are active only against virus that has already infected immune system cells, PRO 542 is designed to neutralize HIV before the virus can enter and infect cells. In previously reported Phase I/II studies in HIV-infected patients, intravenously administered PRO 542 mediated dose-dependent and statistically significant reductions in plasma HIV RNA, a measure of HIV viral load. PRO 542 is currently in Phase II clinical testing.